- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Treatment
Medical Care
Medical disorders, psychiatric disorders, and stress may precipitate or aggravate parasomnias. A careful history of psychosocial stresses, alcohol or drug use, and symptoms of depression should be obtained. Also, a detailed Mental Status Examination should be performed. Patients found to have an underlying psychological or psychiatric disorder should be seen by a psychologist or psychiatrist, and appropriate therapy should be offered.
- The treatment of parasomnias is aimed at lessening the frequency and/or intensity of the events.
- Whether any of the disorders responds better to one of the commonly used agents than another remains unclear.
- The treatment of rapid eye movement behavior disorder is as follows:
- Treatment for REM behavior disorder is initiated with clonazepam at 0.5-1.5 mg taken at bedtime. This medication has been shown to be beneficial in the long-term. Drug discontinuation often results in prompt relapse. The exact mechanism of action of clonazepam in patients with REM behavior disorder is not known, but its serotonergic properties may inhibit nocturnal motor activity in the brainstem and thus prevent arousals.
- Tricyclic antidepressants occasionally are used in the treatment of REM behavior disorder.
- Imipramine, which has serotonergic effects, has been used in the treatment of REM behavior disorder, but the effects are unpredictable.
- Anecdotal reports of levodopa/carbidopa, gabapentin, and clonidine have been published, but the benefit of these drugs has not been systemically evaluated.
- Restless leg syndrome and periodic limb movement disorder are treated with 3 classes of medications. Treatment guidelines are as follows:
- Anti-Parkinson medications, such as levodopa/carbidopa, bromocriptine, and pramipexole (Mirapex), have been used.
- Benzodiazepines, such as diazepam, clonazepam, temazepam, and lorazepam, also have been used.
- Opiates, such as codeine, oxycodone, methadone, and propoxyphene, are other drugs that have been used.
- Several studies have reported efficacy of different medications belonging to the aforementioned groups, but comparative studies between various classes of drugs or even individual drugs do not exist. Therefore, patients should receive one agent, and, if no response is noted, they should be placed on another agent of the same or a different class.
- A combination of drugs may be required in more severe cases. Some patients who do not respond to benzodiazepines alone, levodopa alone, or a combination of both may be treated with opiates.
- Patients should receive the smallest possible doses and should be closely observed for the development of dependency. Accumulated experience dictates that the incidence of abuse, tolerance, or addiction to opiates or benzodiazepines in patients with severe RLS appears to be insignificant. The disabling condition of severe RLS must be treated aggressively.
- RLS and PLMD are chronic conditions that require long-term pharmacologic therapy. Some patients may develop symptoms of restless legs during the daytime, and this may be treated with controlled release of levodopa/carbidopa administered in the evening and morning.
- Effect of levodopa (L-dopa) in the treatment of RLS has been confirmed by a large number of studies. However, most patients on levodopa, after some time, develop a consequence called augmentation. Augmentation is when RLS symptoms appear earlier during the day and involve new parts of the body with increasing severity. Several studies have now confirmed that dopamine agonists can also be effective in RLS and PLMD with less risk for augmentation.
The American Academy of Sleep Medicine made recommendations for the treatment of RLS and PLMD with dopaminergic drugs as follows: levodopa with decarboxylase inhibitor, and the dopaminergic agonists pergolide (withdrawn from US market March 29, 2007), pramipexole, and ropinirole are effective in the treatment of RLS and PLMD. Other dopamine agonists (talipexole, cabergoline, piribidel, and alpha-dihydroergocryptine) and the dopaminergic agents amantadine and selegiline may be effective in the treatment of RLS and PLMD, but the level of effectiveness of these medications is not currently established. No specific recommendations can be made regarding dopaminergic treatment of children or pregnant women with RLS or PLMD. - Avoidance of certain drugs, such as tricyclic antidepressants, fluoxetine, or lithium, may be helpful because these generally worsen the symptoms of RLS and PLMD.
- A decrease in body iron stores, as indicated by serum ferritin levels of less than 50 mcg/L, should be corrected with iron supplementation. Oral iron is preferred but takes a long time, because gastrointestinal absorption is low. However, replenishment is an effective treatment strategy for iron-deficiency anemia and may also relieve RLS and PLMD symptoms (if present).
- Behavioral treatments, such as relaxation therapy, biofeedback, and stress reduction, may be helpful, although they are not universally effective.
- Several studies have reported that levodopa is effective in treating RLS and PLMD.
- An oral dose of 50-100 mg, controlled-release formulation, is prescribed as initial therapy for RLS.
- For PLMD, a controlled-release preparation of levodopa combined with a decarboxylase inhibitor (carbidopa) at a dose of 50-100 mg is begun.
- A dose increase not to exceed 200 mg may be required to completely suppress RLS and PLMD.
- The major adverse effects of levodopa therapy are (1) rebound of symptoms during the daytime and (2) tardive dyskinesia, which is extremely uncommon.
- For rebound symptoms during the daytime, or for augmentation, patients can be treated with dopamine agonists (eg, pramipexole), anticonvulsants (eg, gabapentin, carbamazepine), or benzodiazepines (diazepam, lorazepam).
- Tardive dyskinesia with use of levodopa is uncommon but may occur. The probable mechanism is denervation supersensitivity, which usually occurs in patients with Parkinson disease.
- Dopamine agonists (eg, pramipexole) cause fewer problems compared with levodopa and have become first-line drugs in the treatment of RLS and PLMD.
- In RLS patients refractory to therapy, opioids have been effective; however, such patients must be monitored for addictive behavior.
- Oral repletion with ferrous sulfate at 640–960 mg per day in patients who have reduced iron stores.
Surgical Care
It is not indicated in the treatment of parasomnias.
Consultations
- Consultation with a medical specialist or psychiatrist is indicated for the treatment of underlying conditions that may precipitate the symptoms of the parasomnias.
- Consultation with a hypnotherapist may be of use for patients with sleep disorders. Hypnotherapy has been found to be a cost-effective and noninvasive treatment in adults with sleepwalking and sleep terrors.
Activity
- In general, no reason exists to restrict or change the patient's activity when a parasomnia has been diagnosed; however, certain precautions are valuable in the treatment of sleepwalking.
- Remove potentially dangerous items.
- Locate the bedroom on the ground floor if possible.
- Lock the doors and windows.
- Cover glass windows with heavy drapes.
- Place an alarm or bell on the bedroom door.
Medication
The most common drugs used to treat these disorders are benzodiazepines and anticonvulsants. The general aim of medication treatment is to prevent arousal out of sleep or to suppress REM sleep. Currently, no medications are available that are indicated for these disorders; all medications used for these disorders are used off-label.
Benzodiazepines
Help suppress REM sleep and limit arousal.
Diazepam (Valium)
Medication most frequently used in children, especially with night terrors; DOC for parasomnias. Other benzodiazepines also can be used, most commonly, alprazolam or clonazepam.
Adult
Not established; titration of benefits vs adverse effects recommended
Pediatric
Administer as in adults
Other CNS depressing agents may exacerbate depressant effects; some SSRI agents, such as fluoxetine, can prolong half-life
Documented hypersensitivity; narrow-angle glaucoma
Pregnancy
D - Unsafe in pregnancy
Precautions
Caution with other CNS depressants, low albumin levels, or hepatic disease (may increase toxicity)
Alprazolam (Xanax)
Second choice in this category for parasomnias. Advantages are its brief duration of action and decreased likelihood of morning effects (eg, grogginess). Disadvantages include potential for exacerbating symptoms at lower doses when effects attenuate, owing to possible rebound.
Adult
Not established; titration of benefits vs adverse effects recommended
Pediatric
Administer as in adults
Carbamazepine and disulfiram decrease effects; toxicity increases with cimetidine, lithium, contraceptives, and CNS depressants (including alcohol)
Documented hypersensitivity; severe respiratory depression, narrow-angle glaucoma, preexisting hypotension
Pregnancy
D - Unsafe in pregnancy
Precautions
Withdrawal symptoms, including seizures, may occur upon abrupt discontinuation
Clonazepam (Klonopin)
Similar to alprazolam, it is a good alternative option to diazepam. Advantages are the presumed specificity for CNS GABA receptors. Disadvantages include potential for exacerbating symptoms at lower doses when effects attenuate, owing to possible rebound.
Adult
Not established; titration of benefits vs side effects recommended
Pediatric
Not established
Phenytoin and barbiturates may reduce effects; coadministration of CNS depressants increase toxicity
Documented hypersensitivity; severe liver disease and acute narrow-angle glaucoma
Pregnancy
D - Unsafe in pregnancy
Precautions
Caution in chronic respiratory disease or impaired renal function; withdrawal symptoms can result from abrupt discontinuation of the medication
Anticonvulsants
Agents in this drug category inhibit arousal.
Carbamazepine (Tegretol, Carbatrol)
Most commonly used agent for these disorders, but anecdotal evidence supports the possible use of GABA-enhancing agents such as valproate (Depakene, Depakote) or gabapentin (Neurontin). With respect to all of these agents, both hs dose alone and titration (as for epilepsy) has been reported.
Adult
Not to exceed 400 mg PO hs; titrate according to monotherapy levels of this agent
Pediatric
Not established; 10-20 mg/kg/d PO in divided doses suggested; titrate by levels to monotherapy doses
Do not coadminister with MAOIs; cimetidine may increase toxicity, especially if taken in first 4 wk of therapy; may decrease blood levels of a number of other drugs, including valproic acid and phenytoin, through its effect on the cytochrome P-450 enzyme system; however, also can increase effects of other CNS depressant agents through its CNS effects
Documented hypersensitivity; history of bone marrow depression; administration of MAOIs within last 14 d
Pregnancy
D - Unsafe in pregnancy
Precautions
Do not use to relieve minor aches or pains; caution with increased intraocular pressure; obtain CBCs and serum iron baseline prior to treatment, during first 2 mo, and yearly or every other year thereafter; can cause drowsiness, dizziness, and blurred vision; caution while driving or performing other tasks requiring alertness
Valproate (Depakene, Depakote)
As with other drugs in this category, both hs and standard doses have been reported to be useful in treating parasomnias.
Adult
No standard information available; doses not to exceed 1000 mg PO hs may be given
For standard titration, administer 10-15 mg/kg/d, not to exceed 60 mg/kg/d as initial dose
Pediatric
Not established; base dosing on epilepsy and migraine, similar limits of mg/kg/d dosing advised
For single hs dosing, likewise, no information available
Coadministration with cimetidine, felbamate, and erythromycin may increase toxicity by increasing valproate levels; rifampin may significantly reduce levels; in pediatric patients, protein binding and metabolism of valproate decrease when taken concomitantly with salicylates; coadministration with carbamazepine may result in variable changes of carbamazepine concentrations, with possible loss of seizure control; valproate may increase diazepam and ethosuximide toxicity (monitor closely)
May increase phenobarbital and phenytoin levels while either one may decrease valproate levels; valproate may displace warfarin from protein-binding sites (monitor coagulation tests); may increase zidovudine levels in HIV seropositivity; because of its effects on platelets, should be used with caution with aspirin and other antiplatelet agents
Coadministration with lamotrigine may result in an increased risk of Stevens-Johnson syndrome when standard dose titration of lamotrigine is used
Documented hypersensitivity; hepatic disease/dysfunction
Pregnancy
D - Unsafe in pregnancy
Precautions
Thrombocytopenia and abnormal coagulation parameters have occurred; the risk of thrombocytopenia increases significantly at total trough valproate plasma concentrations of >110 mcg/mL in females and 135 mcg/mL in males; at periodic intervals and prior to surgery, determine platelet counts and bleeding time before initiating therapy; reduce dose or discontinue therapy if hemorrhage, bruising, or a hemostasis/coagulation disorder occurs; hyperammonemia may occur, resulting in hepatotoxicity; monitor patients closely for appearance of malaise, weakness, facial edema, anorexia, jaundice, and vomiting; may cause drowsiness; should abdominal/GI symptoms develop, consideration also should be given to the possibility of pancreatitis
Gabapentin (Neurontin)
Has not been used as frequently as the other 2 anticonvulsants, and information is less available. As with the other 2 agents in this category, no information is available nor consensus reached regarding the use of hs dosing vs standard antiepileptic dosing.
Adult
Not established; 300 mg PO tid suggested; titrate to 3600 mg/d in divided doses; not to exceed 1200 mg/dose
Pediatric
Not established
Antacids may significantly reduce bioavailability (administer > 2 h following antacids)
Documented hypersensitivity
Pregnancy
C - Safety for use during pregnancy has not been established.
Precautions
Caution in severe renal disease
Antiparkinsonian drugs
Very effective for RLS and PLMD. Sinemet CR is the most commonly used drug, but pergolide and pramipexole also are effective. Pergolide was withdrawn from the US market March 29, 2007, because of heart valve damage resulting in cardiac valve regurgitation. It is important not to abruptly stop pergolide. Health care professionals should assess patients' need for dopamine agonist (DA) therapy and consider alternative treatment. If continued treatment with a DA is needed, another DA should be substituted for pergolide. For more information, see FDA MedWatch Product Safety Alert and Medscape Alerts: Pergolide Withdrawn From US Market.
Levodopa and carbidopa (Sinemet CR)
Large neutral amino acid absorbed in proximal small intestine by saturable carrier-mediated transport system. Absorption is decreased by meals that include other large neutral amino acids. Only patients with meaningful motor fluctuations need to consider a low-protein or protein-redistributed diet. Greater consistency of absorption achieved when levodopa taken 1 h or more pc. Nausea often is reduced if levodopa taken immediately following meals. Some patients with nausea benefit from additional carbidopa in doses not to exceed 200 mg/d. Half-life of levodopa/carbidopa is approximately 2 h.
Most common acute adverse effects are nausea, hypotension, and hallucinations. Long-term adverse effects include motor fluctuations and dyskinesia (chorea)
Provide at least 70-100 mg/d carbidopa. When more carbidopa is required, substitute one 25/100-tab for each 10/100-tab. When more levodopa is required, substitute 25/250-tab for the 25/100-tab or 10/100-tab.
The SR formulation of levodopa/carbidopa is absorbed more slowly and provides more sustained levodopa levels than the IR form. It is as effective as IR formulation when levodopa is initially required and may be more convenient when fewer intakes are desired.
Patients with dissipating motor fluctuations (and no dyskinesia) often benefit from prolongation of short-duration response when switched from IR to CR levodopa/carbidopa. However, patients with meaningful fluctuations and dyskinesia often experience an increase in dyskinesia when switched to the CR formulation.
Adult
Slow-release preparation: 100/25 mg PO 1 h before hs; may be doubled if indicated
Pediatric
Not established
Hydantoins, pyridoxine, phenothiazine, and hypotensive agents may decrease effects of levodopa; levodopa toxicity increases with antacids and MAOIs
Documented hypersensitivity; narrow-angle glaucoma, malignant melanoma, or undiagnosed skin lesions
Pregnancy
D - Unsafe in pregnancy
Precautions
Certain adverse CNS effects (eg, dyskinesias) may occur at lower dosages and earlier in therapy with SR form; caution in patients with history of myocardial infarction, arrhythmias, asthma, and peptic ulcer disease; sudden discontinuation of levodopa may cause worsening of Parkinson disease; high-protein diets should be distributed throughout the day to avoid fluctuations in levodopa absorption
Pergolide (Permax)
Pergolide was withdrawn from the US market. Believed to exert therapeutic effect by directly stimulating postsynaptic dopamine receptors in nigrostriatal system. Usually administered in divided doses tid. During dosage titration, dosage of concurrent levodopa/carbidopa may be cautiously decreased.
Adult
0.05 mg PO hs for first 2 d initially; gradually increase by 0.05 mg/d q3d over next 12 d, followed by increments of 0.25 mg/d q3d until optimal therapeutic dosage is achieved, generally 0.25-0.5 mg is effective
Pediatric
Not established
Dopamine antagonists (eg, neuroleptic phenothiazines, butyrophenones, thioxanthenes, or metoclopramide) may diminish effectiveness of pergolide, a dopamine agonist; because pergolide mesylate is >90% bound to plasma proteins, exercise caution if coadministered with other drugs known to affect protein binding
Documented hypersensitivity
Pregnancy
C - Safety for use during pregnancy has not been established.
Precautions
Caution in cardiac dysrhythmias; may cause or exacerbate preexisting states of confusion and hallucinations or dyskinesia
Pramipexole (Mirapex)
Although used for Parkinson disease, has been found to be beneficial in RLS and PLMD.
Nonergot dopamine agonist with specificity of the D2 dopamine receptor, but also has been shown to bind to D3 and D4 receptors and possibly may stimulate dopamine activity on the nerves of striatum and substantia nigra.
Adult
Week 1: 0.125 PO mg hs
Week 2: 0.25 mg PO hs
Week 3: 0.5 mg PO hs
Pediatric
Not established
Cimetidine may increase toxicity; levodopa levels are increased with concurrent use
Documented hypersensitivity
Pregnancy
C - Safety for use during pregnancy has not been established.
Precautions
Caution in renal insufficiency and preexisting dyskinesias
Opiates
Opiates such as codeine, propoxyphene, and dihydromorphone have been used in patients who have severe RLS who do not benefit from other therapy. Patients should be closely observed for development of tolerance and dependency.
Propoxyphene (Darvon)
Drug combination indicated for severe RLS. Binds to opiate receptors in CNS, causing inhibition of ascending pain pathways, altering perception and response to pain
Adult
1-2 tab (15-30 mg) PO hs
Pediatric
Not established
Toxicity increases with concurrent administration of tricyclic antidepressants, MAOIs, neuromuscular blockers, CNS depressants, phenothiazines, and narcotic analgesics; may increase serum concentrations of MAOIs, tricyclic antidepressants, carbamazepine, phenobarbital, and warfarin
Documented hypersensitivity; HACE diagnosis; elevated ICP
Pregnancy
C - Safety for use during pregnancy has not been established.
Precautions
Use to treat cough in patients with HAPE only if absolutely necessary; may depress hypoxic ventilatory rate and respiratory drive during sleep; caution in patients dependent on opiates, substitution may result in acute opiate withdrawal symptoms; caution in severe renal or hepatic dysfunction
More on Parasomnias |
| Overview: Parasomnias |
| Differential Diagnoses & Workup: Parasomnias |
 Treatment & Medication: Parasomnias |
| Follow-up: Parasomnias |
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Further Reading
Keywords
nightmare disorder, sleep terror disorder, sleepwalking disorder, rapid eye movement sleep behavior disorder, REM sleep behavior disorder, non–rapid eye movement, NREM, restless legs syndrome, RLS, periodic limb movement disorder, PLMD, dyssomnias, sleep drunkenness, microsleeps
